A new approach for achieving enhanced immunogenicity of proteins and peptides through structural modification was recently discovered in our laboratory. This structural modification involves substitution of carboxylic groups of proteins and peptides by amino groups. Cell membranes are predominantly made up of negatively charged groups to which extrinsic proteins stick by electrostatic interaction. Increase in positive charges promotes antigen binding to antigen presenting cells. In this study, we shall systemically investigate immunogenicity of proteins and peptide antigens prepared by such substitution. Antigens tested will be bovine serum albumin, bovine serum albumin peptides, ovalbumin and tetanus toxoid. We shall immunize low and high responder strains of mice and measure immune response by determining levels of antibodies produced as a result of antigenic stimulation. Animals will be immunized with and without adjuvant by parenteral and oral routes. We shall analyze modifications carried out on the antigen molecules by substitution and relate them to the increase in immunogenicity and to the uptake and binding of the antigens. We shall also investigate the mechanism of enhanced immunogenicity by examining the processing and presentation of these antigens to T helper and suppressor cells, which are the major regulators of immune responsiveness. Our approach to increase immunogeneicity through structural modification is a new concept. Unlike traditional adjuvants, there is antigen specific enhancement without additional reagents which possibly produce unwanted side effects. Experimental data recently obtained in our laboratory (published and in press) provide substantial evidence that our approach may prove to be superior in the development of new vaccines.